In May, PhD students who are funded by the Medical Research Council (MRC) were invited to enter the Max Perutz science writing award 2021 and write a compelling piece about their research for the non-scientific reader.
From the many entries received, the 10 that made the shortlist covered diverse topics, including dementia, childhood adversity, the role of genes in schizophrenia and the use of hypnosis to treat psychosis.
The essays were judged by: the Observer’s Ian Tucker, the Science Museum’s science director, Roger Highfield; Prof Fiona Watt, executive chair at the MRC, Andy Ridgway, senior lecturer in science communication at the University of the West of England in Bristol, the author and broadcaster Gaia Vince, and the researcher and mental health advocate Dr Furaha Asani.
At a virtual ceremony last month, the £1,500 prize was presented to the winner, Vicky Bennett from the University of Bath, for her article about her research into repurposing drugs to treat urinary tract infections.
Here we publish the winning article, described by Roger Highfield as “a gallant way to make unglamorous research interesting.”
The winning essay
I’m a biomedical research scientist. My laboratory essentials are a white coat, bubbling liquid, and the occasional explosion. I make groundbreaking discoveries every day. Crowds gather to marvel at my experiments and their life-saving implications.
This is at least my mum’s impression of my PhD so far.
The reality of my current situation seems somewhat different. My shiny white lab coat was at first a wonderful addition to my wardrobe, but the many tanks of infected urine on my workbench are far from glamorous. (In fact, shiny white lab coat + infected urine = smelly yellow lab coat). Instead of crowds of admirers, “the wee area” of our shared lab space is actively avoided. The consequences of any kind of explosion are not worth contemplating.
Welcome to the world of urinary tract infection research.
Urinary tract infections (UTIs) are not particularly pleasant. They occur when bacteria from poo come into contact with and enter the external opening of the urethra, the tube that allows urine to flow from the bladder to the outside of the body. If bacteria colonise the urethra, they then have direct access to the bladder. This is the ideal environment for them to multiply and spread upwards to infect the kidneys, or even enter the bloodstream.
For those lucky enough not to have experienced a UTI, the frequent urge to urinate and a painful stinging or burning sensation when passing urine are characteristic symptoms. UTIs are common for all ages, but obvious anatomical differences mean that women are more frequent sufferers, as a shorter urethra reduces the distance bacteria must travel to reach the bladder. With up to 60% of adult women suffering at least one UTI in their lifetime (compared to 12% of men), many see them as an awkward but inevitable part of life. Data on transgender experience of UTIs is limited, but advice sites report they can be an issue for genital tuckers and trans men taking testosterone. Sufferers have even gone so far as to describe their experiences in song form. See Love song for my UTI by YouTuber Lex Croucher for one of my favourite examples.
A short course of antibiotics will clear most infections. But the number of bacteria resistant to antibiotics is increasing. Someone with an infection which was once curable in a few days may now try several different antibiotics before finding one that works. And even if your symptoms do clear up, it may be that the bacteria have not been fully eradicated, with around 30% of infections returning within six months. Many people must accept a life of chronic recurring UTIs and near-permanent symptoms.
Every UTI also has the risk of developing into a life-threatening kidney or bloodstream infection. This risk increases with age, and for those with underlying health conditions. The ever-growing threat of antibiotic resistance means that chronic and severe infections are becoming more common. Even that well known mythical cure that is cranberry juice will not have any effect against multidrug-resistant bacteria.
So, the solution is to find some new, better antibiotics, right? Something that kills bacteria quickly and is hard for bacteria to become resistant to. This essentially is the aim of my PhD project. I am trying to identify specific parts of bacteria that would make good targets for new antibiotics to attack. I will then use a computer modelling system to identify existing drugs which could be used in a new way to hit these targets and kill the bacteria. These come from huge databases of millions of drugs used for any purpose in medicine, not necessarily existing antibiotics. This is a process called drug repurposing. If successful it will reduce the time and cost associated with new antibiotic development.
This leads us back to my urine tanks. In my research group we work with a bacteria called Proteus mirabilis, a common cause of catheter-associated urinary tract infections (CAUTIs). Urinary catheters are the most commonly used medical devices. The catheter is a long flexible tube inserted through the urethra into the bottom of the bladder and is connected to a urine collection bag outside the body. They are used in people of all genders with medical conditions that make it hard for the bladder to empty naturally, as well as before or after some types of surgery. Depending on the situation, the catheter could be temporary or permanent.
But the presence of a catheter makes it easier for UTIs to develop. Bacteria grow much more easily on the catheter surface, and the tube provides a direct pathway for them to enter the urethra and the bladder. As the bacteria build up, they will eventually block the tube and prevent urine leaving the bladder. This causes urine to collect in the bladder, where it can flow backwards towards the kidneys, increasing the likelihood of life-threatening kidney and bloodstream infections, as well as causing a huge amount of pain from the urinary retention itself.
We recreate this situation in the lab by using catheters inserted into replica glass bladders. A pump system pushes urine through the bladder and into the catheter at body temperature so we can monitor the effects of our experiments in as realistic a way as possible. We infect the glass bladder and leave the bacteria to grow on the catheter surface, where the buildup of bacteria will eventually block the tube and stop urine from entering the collection bag.
A key aspect of these experiments is reproducibility and reliability of results. Real urine is very variable depending on what someone has been eating or drinking, therefore I spend a day each week making up five-litre tanks of artificial urine to use in my experiments to ensure consistency. This involves mixing water with urea and various salts such as potassium and sodium chloride. It even smells like the real thing.
The time taken for the catheter to block determines the success of different drugs. These could be tested in several ways: either by being flushed into the bladder through the catheter, dissolved in the urine, or applied as a coating to the catheter before it is inserted. The longer the time to catheter blockage, the more promising the treatment. And you would not believe the anticipation and excitement caused by watching urine slowly drip through a bacteria-encrusted catheter.
Of course I am not yet 12 months into my three-and-a-half-year project, and there is a long, long way to go before handing a patient a drug which will cure their infection. However, I really hope that my research will support the development of new antibiotic treatments to help patients with CAUTIs, chronic UTIs not treatable with existing drugs, and anyone who is fed up with that burning sensation when they pee.
Source: Cranberry juice won’t cut it: UTIs and the potential for repurposing drugs